ArticleTranslational psychiatry2019
Estradiol modulation of the renin-angiotensin system and the regulation of fear extinction.
Article in Translational psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- Changes in dorsomedial striatum activity during expression of goal-directed vs. habit-like cue-induced cocaine seeking.Addiction neuroscience · 2024Article
- Acute Angiotensin II Receptor Blockade Facilitates Parahippocampal Processing During Memory Encoding in High-Trait-Anxious Individuals.Biological psychiatry global open science · 2024Article
- The central renin-angiotensin system: A genetic pathway, functional decoding, and selective target engagement characterization in humans.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Estradiol-mediated small GTP-binding protein GDP dissociation stimulator induction contributes to sex differences in resilience to ferroptosis in takotsubo syndrome.Redox biology · 2023Article
- Sex-dependent effects of angiotensin II type 1 receptor blocker on molecular and behavioral changes induced by single prolonged stress.Behavioural brain research · 2023Article
- The Renin Angiotensin System as a Therapeutic Target in Traumatic Brain Injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- Sex differences in fear responses: Neural circuits.Neuropharmacology · 2023Review
- Involvement of the brain-heart axis in the link between PTSD and cardiovascular disease.Depression and anxiety · 2022Review
- AT1 Receptors: Their Actions from Hypertension to Cognitive Impairment.Cardiovascular toxicology · 2022Review
- Hypothalamic-pituitary-adrenal axis and renin-angiotensin-aldosterone system in adulthood PTSD and childhood maltreatment history.Frontiers in psychiatry · 2022Article
- Involvement of the Renin-Angiotensin System in Stress: State of the Art and Research Perspectives.Current neuropharmacology · 2022Review
- Sex-Related Predisposition to Post-Traumatic Stress Disorder Development-The Role of Neuropeptides.International journal of environmental research and public health · 2021Review
- Limbic Neuropeptidergic Modulators of Emotion and Their Therapeutic Potential for Anxiety and Post-Traumatic Stress Disorder.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Review
- Evaluation of an angiotensin Type 1 receptor blocker on the reconsolidation of fear memory.Translational psychiatry · 2020Article
- The neurobiological basis of sex differences in learned fear and its inhibition.The European journal of neuroscience · 2020Review
- Pharmacotherapy of anxiety disorders in the 21st century: A call for novel approaches.General psychiatry · 2019Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Post-traumatic stress disorder (PTSD) is more prevalent in women than men, yet much remains to be determined regarding the mechanism underlying this sex difference. Clinical and preclinical studies have shown that low estradiol levels during extinction of fear conditioning in rodents (i.e., cue exposure therapy in humans) leads to poor extinction consolidation and increased fear during extinction recall. The renin-angiotensin system (RAS) is also associated with stress-related pathologies, and RAS antagonists can enhance extinction consolidation in males. However, less is known about how estradiol and the RAS converge to alter fear extinction consolidation in females. Since estradiol downregulates the RAS, we determined the role of surgically (via ovariectomy [OVX]) and pharmacologically (via the hormonal contraceptive [HC], levonorgestrel) clamping estradiol at low levels in female rats on fear-related behavior, serum estradiol and angiotensin II (Ang II) levels, and angiotensin II type I receptor (AT1R) binding in the brain. We then tested whether the AT1R antagonist losartan would alter fear-related behavior in an estradiol-dependent manner. We found that both OVX and HC treatment produced extinction consolidation deficits relative to intact female rats in proestrus (when estradiol levels are high), and that losartan treatment mitigated these deficits and reduced freezing. OVX, but not HC, altered AT1R ligand binding, though HC reduced estradiol and increased Ang II levels in plasma. These findings have significant clinical implications, indicating that administration of an AT1R antagonist, especially if estradiol levels are low, prior to an exposure therapy session may improve treatment outcomes in females.
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